Environmental pollution is one of the most serious challenges to human health. Chronic exposure to pollutants accompanied by continued reactive oxidative species (ROS) production can lead to oxidation of cellular molecules and consequent promotion of oxidative stress. Cross-linking is often seen in ROS-induced protein oxidation, and accumulation of unwanted protein cross-links has been associated with aging and the progression of many human diseases. As a barrier between the organism and the environment, the skin is directly and constantly exposed to environmental oxidants, such as ultraviolet light (UV) radiation, tobacco smoke, and air pollution. Prolonged or repetitive exposure to these environmental oxidants can lead to the development or exacerbation of various cutaneous diseases. In this study, we used cultured epidermal keratinocytes as a model to investigate the adverse effects of environmental oxidants toward the skin. In Chapter One, we reported the phenomenon of protein cross-linking mediated by pro-oxidants, such as carbonyls, in woodsmoke extracts. Our results suggest that oxidative cross-linking of cellular proteins could alter the cell proteome and function, revealing an action through which air pollution can negatively impact the skin. In Chapter Two, we performed proteomic analysis on cells exposed to three types of environmental ROS generators, including 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), mesquite liquid smoke (MLS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to characterize and identify proteins that are susceptible to oxidative damage. Finally, in Chapter Three, we developed and optimized a culture system for epithelial cells from white and green sturgeon to test the sensitivity of these endangered species to environmental pollutants.